title: Losartan protects mesenteric arteries from ROS-associated decrease in myogenic constriction following 5/6 nephrectomy.
abstract: BACKGROUND
  Chronic renal failure (CRF) is associated with hypertension, proteinuria, loss of myogenic constriction (MC) of mesenteric arteries and increased production of reactive oxygen species (ROS) under experimental conditions. Previous results showed that ACE (angiotensin-converting enzyme activity) inhibitor therapy is effective in slowing down the progression of disease. Therefore, we wanted to study whether the inverse AT(1) (angiotensin II type 1) receptor agonist, losartan (LOS) was effective in preventing loss of MC in a rat model of CRF and whether acute ROS scavengers could improve MC.
  
  
  METHODS
  Rats underwent 5/6 nephrectomy (5/6 Nx) and were treated with vehicle or LOS (20 mg/kg/day; 5/6 Nx + LOS) for 12 weeks. Thereafter, the MC of the mesenteric arteries were measured in the presence and/or absence of tempol and catalase. Systolic blood pressure and proteinuria were measured weekly.
  
  
  RESULTS
  Systolic blood pressure and proteinuria in the 5/6 Nx + LOS group were significantly lower than in the 5/6 Nx group. Moreover, the MC of 5/6 Nx + LOS arteries was significantly increased compared with the untreated 5/6 Nx group (maximum MC, 32.3 ± 6.9 vs 8.9 ± 3.8% (p < 0.01)). Tempol + catalase significantly increased the MC in the 5/6 Nx group, but not in the 5/6 Nx + LOS group (increase in MC, 59.7 ± 13.0 (p < 0.05) vs. 17.0 ± 15.1%).
  
  
  CONCLUSIONS
  These results support the roles of the RAAS (renin-angiotensin-aldosterone system) and ROS in the vascular dysfunction of systemic vessels in CRF.
authors.affiliation: Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, Groningen, The Netherlands. p.vavrinec@med.umcg.nl
authors.forename: Peter
authors.initials: P
authors.lastname: Vavrinec
authors.forename: Richard Pe
authors.initials: RP
authors.lastname: van Dokkum
authors.forename: Maaike
authors.initials: M
authors.lastname: Goris
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
authors.forename: Robert H
authors.initials: RH
authors.lastname: Henning
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology; D009119:Muscle Contraction / Q000187:drug effects*; D009392:Nephrectomy; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016166:Free Radical Scavengers; D020011:Protective Agents; D017382:Reactive Oxygen Species; D019808:Losartan; D000109:Acetylcholine